Role of newly identified lung tissue protective factors in chronic obstructive pulmonary disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04180
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: Sugiura Hisatoshi 東北大学, 医学系研究科, 教授 (20445092)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 活性硫黄分子種 / 抗老化因子 / 転写因子

Outline of Final Research Achievements

In the current project, we aimed to investigate the roles of newly identified lung tissue protective factors including reactive sulfur species (RSS), growth differentiation factor 11 (GDF11), and LXH9 in the pathogenesis of chronic obstructive pulmonary disease (COPD). We found that production of RSS in the COPD lungs was significantly decreased compared to those in the control subjects. In the RSS synthetase knockout mice, more airspace enlargement induced by elastase in the lungs was observed, while RSS donor significantly improved the elastase-induced emphysema in mice. Anti-aging factor, GDF11 was also decreased in the lungs and serum from the COPD patients compared with healthy subjects. The levels of serum GDF11 in the COPD patients significantly associated with the data of lung function and physical activity. Upregulation of LHX9 in type II pneumocytes was observed in the COPD patients and LHX9 was associated with cell death of type II pneumocytes.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

COPDの病態は不明な点が多く、とりわけ肺の保護因子の観点からの研究は少ない。本研究で明らかにした活性硫黄分子種は全く新規の内因性抗酸化分子でありヒト肺に存在し、COPD患者肺においてその産生量が低下しており、肺の保護作用を有することを世界で初めて明らかにした。また、COPD患者におけるGDF11の産生低下は、COPDの分子病態のみならず臨床病態とも関連することが明らかになった。LHX9は有望な転写因子でその阻害は肺気腫の進展に貢献する可能性がある。